Blood glucose control is a primary goal when treating individuals with type 2 diabetes. Glucose control alone, however, does not eliminate a diabetic's risk for vascular complications or vascular diseases. Vascular complications and vascular diseases impair the ability of the arteries in the circulatory system in general and the coronary arteries in particular to expand (vasodilate) and contract (vasoconstrict). Vascular complications represent the most severe manifestations of type 2 diabetes. For example atherosclerosis of the coronary, cerebral, and peripheral arteries is 24 times more prevalent in individuals with diabetes compared to non-diabetics and these conditions occur earlier and progress more rapidly in diabetics. The primary vascular complications of a diabetic include an increased incidence of lower limb ischema and neuropathy (which can lead to amputation), kidney disease, heart attack, and retinopathy (which can lead to blindness). In addition, when individuals with diabetes develop clinical vascular disease, they sustain a worse prognosis for survival than do individuals without diabetes. Although dietary control of blood glucose is a primary goal for individuals with diabetes, glucose control alone does not completely offset the increased risk for vascular disease.
The underlying metabolic cause of type 2 diabetes is the combination of impairment in insulin-mediated glucose disposal (insulin resistance) and/or defective secretion of insulin by pancreatic cells, i.e., people with type 2 diabetes no longer use or secrete insulin properly. The accelerated development of the vascular complications in type 2 diabetics is the result of a combination of insulin resistance and the non-random clustering of risk factors that accompany insulin resistance. These risk factors include hypertension (up to 75% of vascular disease occurs in diabetic individuals with hypertension), increased levels of more atherogenic lipoproteins (small dense LDL and triglyceride-rich lipoproteins), low levels of HDL cholesterol, and elevated levels of hemostatic (blood clotting) factors and C-reactive protein (a marker of inflammation). Collectively, these conditions, which cluster in diabetic individuals, can lead to damaged or impaired vascular endothelial cell function and accelerated vascular disease. Thus, treatments that both promote blood glucose tolerance and reduce a diabetic's risk for vascular diseases are desirable.
Such treatments may include diets that attempt to control and optimize the intake of certain dietary components such as fatty acids. Fatty acids are carboxylic acids and are classified based on the length and saturation characteristics of the carbon chain. Short chain fatty acids have 2 to about 4 carbons and are typically saturated. Medium chain fatty acids have from about 6 to about 10 carbons and are also typically saturated. Long chain fatty acids have from about 12 to about 24 or more carbons and may also be saturated or unsaturated. In longer fatty acids there may be one or more double bonds (unsaturation), giving rise to the terms “monounsaturated” and “polyunsaturated”, respectively.
Longer chain lipids are categorized according to the number and position of double bonds in the fatty acids according to a nomenclature well understood by the biochemist Biochemists often group long chain polyunsaturated fatty acids (LCPUFA) into series or families based on the position of the double bond in the carbon chain. The family to which an LCPUFA belongs is determined by the position of the double bond closest to the methyl end of the fatty acid. For example, the omega-3 series (or n-3 series) contains a first double bond at the third carbon from the methyl end of the fatty acid, the omega-6 series (or n-6 series) contains its first double bond at the sixth carbon, and the omega-9 series (or n-9 series) has no double bond until the ninth carbon. Alpha-linolenic acid, for example, has a chain length of 18 carbons and has 3 double bonds with the first double bond from the 25 methyl end located at the third carbon making it a member of the omega-3 family. A short hand nomenclature has been developed to provide all this information about a fatty acid at a glance. The nomenclature is: [chain length]:[number of double bonds]n-[position of the double bond closest to the methyl end of the fatty acid]. Thus, alpha-linolenic acid (ALA) is referred to as “C18:3n-3”. Similarly, docosahexanoic acid (DHA) has a chain length of 22 carbons with 6 double bonds beginning with the third carbon from the methyl end and, thus, is designated “C22:6n-3”. Another LCPUFA is eicosapentaenoic acid (EPA) which is designated “C20:5n-3”.
Diets rich in omega-3 fatty acids have been associated with a low incidence of type 2 diabetes. Studies have mostly focused on the omega-3 fatty acids EPA (C20:5n-3) and DHA (C22:6n-3), which are found in marine oils. ALA (C18:3n-3) is another omega-3 fatty acid that has not been studied as intensely as eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA). Alpha-linolenic acid (ALA) can be metabolized in the body to eicosapentaenoic acid and docosahexanoic acid by the multiple enzymatic steps involving enzymes such as desaturase and elongase. Investigations that have been made into the benefit of alphainolenic acid with animal models on diabetics have reported mixed results. For example, two studies have evaluated the effects of alpha-linolenic acid on glucose metabolism in a genetically insulin-resistant animal model. Kato et al., Journal of Health Science 46. 489-492 (2000), found a significant improvement in blood glucose response to insulin in genetically insulin-resistant diabetic mice (KK-Ay) 21 days after daily administration of alpha-linolenic acid by gavage. Hun et al., Biochemical and Biophysical Research Communications 259, 85-90 (1999), fed high fat diets containing perilla oil, which is rich in alpha-linolenic acid, to genetically insulin resistant diabetic mice (KK-Ay). Hun et al. found, in contrast to Kato et al., that blood glucose levels were not significantly different after 8 weeks compared to mice consuming diets with soybean oil, which is rich in omega-6 polyunsaturated fatty acids, or lard, which contains only saturated and monounsaturated fatty acids.
Other studies have evaluated the effect of linseed (flaxseed) oil capsules on glucose metabolism in humans with type 2 diabetes mellitus or insulin resistance. McManus et al., Diabetes Care 19, 463-467 (1996), reported no difference in fasting glucose or insulin levels, or insulin sensitivity after three months for individuals with type 2 diabetes mellitus who had consumed capsules containing either linseed oil or fish oil. Goh et al., Diabetologia 40, 45-52 (1997), reported no differences in fasting glucose or insulin levels after three months when individuals with type 2 diabetes mellitus consumed oil capsules containing linseed oil or fish oil. In contrast, Nestel et al., Arteriosclerosis, Thrombosis, and Vascular Biology 17, 1163-1170 (1996), reported that insulin sensitivity decreased when obese individuals with markers of insulin resistance consumed diets rich in alpha-linolenic acid provided as margarine and muffins made with flaxseed oil.
Several patents disclose the use of lipid profiles containing omega-3, omega-6 and omega-9 fatty acids. For example, U.S. Pat. No. 5,780,451 (the “'451 patent”) to DeMichele et al. discloses a nutritional product for persons with ulcerative colitis that utilizes omega-3, omega-6 and omega-9 fatty acids within specified percentage ranges. The ratio of omega-6 to omega-3 fatty acids of the '451 patent is disclosed as being in the range of 0.25:1 to 4.0:1 (ratios based on weight). Of the several omega-3 fatty acids used in the '451 patent, eicosapentaenoic acid is the most prevalent (with a preferred range based on weight of 16.0% to 19.6%) and alpha-linolenic acid is the least prevalent (with a preferred range based on weight of 1.5% to 2.1%). The specified ratio of linoleic acid to alpha-linolenic acid is in the range of 3.0 to 10.0 (ratios based on weight).
U.S. Pat. No. 4,921,877 to Cashmere et al. discloses a liquid nutritional product for use by glucose intolerant persons. Table 1 of the '877 patent discloses the preferred ingredients which include soy oil, high oleic safflower oil, and soy lecithin. These components create a lipid system containing an omega-9 fatty acid (oleic acid), an omega-6 fatty acid (linoleic acid), and an omega-3 fatty acid (alpha-linolenic acid). The omega-3 component of this system is only present at a relatively low percentage by weight (approximately 1.2% of the lipid system).
Other patents specify an optimal ratio for omega-6 to omega-3 fatty acids, but do not disclose an optimal ratio for omega-9 to omega-3 fatty acids. For example, U.S. Pat. No. 5,308,832 to Garleb et al. discloses a nutritional product for use by persons with a neurological injury. The '832 patent discloses a multi component lipid blend (see Table 8 of the '832 patent) and specifies a ratio of omega-6 to omega-3 fatty acids in the range by % weight of 1 to 6. No preferred ratio of omega-9 to omega-3 fatty acids is disclosed. Also, U.S. Pat. No. 5,922,704 (the “'704 patent”) to Bland discloses nutritional supplements for men. The '704 patent discloses the use of linoleic acid (omega-6) and alpha-linolenic acid (omega-3) in a ratio of 1:2. No preferred ratio of omega-9 to omega-3 fatty acids is disclosed.